Fungicidal hydantoin derivatives

ABSTRACT

THE HYDANTOIN DERIVATIVES F THE FORMULA:   1-(R1-CO-),2-(X=),3-AR,4-(O=),5-R2-IMIDAZOLIDINE   WHEREIN AR REPRESENTS PHENYL, OR PHENYLCARRYING SUBSTITUENTS SELECTED FROM HALOGEN, ALKYL, ALKOXY AND TRIFLUOROMETHYL, R1 REPRESENTS ALKOXY OR GROUPING -MR3R4, IN WHICH R3 AND R4 REPRESENT HYDROGEN, ALKYL OR ALKENYL, R2 REPRESENTS HYDROGEN OR ALKYL, AND X REPRESENTS OXYGEN OR SULPHUR, POSSESS FUNGICIDAL PROPERTIES.

3,823,240 FUNGICIDAL HYDANTOIN DERIVATIVES Michel Sauli, Paris, France,assignor to Rhone- Poulenc S.A., Paris, France No Drawing. Originalapplication Oct. 5, 1971, Ser. No.

186,772, now Patent No. 3,755,350. Divided and this application Jan. 18,197 3, Ser. No. 324,788 Claims priority, application France, Oct. 6,1970, 7036084; Aug. 6, 1971, 7128896 Int. Cl. A01n 9/22 US Cl. 424-273 9Claims ABSTRACT OF DISCLOSURE The hydantoin derivatives of the formula:

(JO-R1 wherein Ar represents phenyl, or phenyl carrying substituentsselected from halogen, alkyl, alkoxy and trifluoromethyl, R representsalkoxy or a grouping --NR R in which R and R represent hydrogen, alkylor alkenyl, R represents hydrogen or alkyl, and. X represents oxygenor'sulphur, possess fungicidal properties.

This is a division of application Ser. No. 186,772, filed I Oct. 5,1971, now Pat. No. 3,755,350.

This invention relates to new hydantoin derivatives 1 which possessfungicidal properties to processes for their preparation and tocompositions containing them.

The hydantoin derivatives of the present invention are compounds of thegeneral formula:

1 wherein Ar represents aphenyl radical or a phenyl radical carrying oneto five substituents, which may be the same or different, selected fromhalogen atoms (preferably chlorine), alkyl and alkoxy radicalscontaining 1 to 4 carbon atoms and the trifluoromethyl radical, Rrepresents an alkoxy radical containing 1 to 4 carbon atoms or agrouping --NR R in which R and R are the same or (wherein Hal'representsa halogen, preferably chlorine,

atom and R is as hereinbefore'defined) with a hydantoin compound of thegeneral formula:

111T T=x ----NAr III wherein Ar, R and X are as hereinbefore defined.Generally the reaction can be carried out in a basic organic solventsuch as' pyridine or in an organic solvent such as benzene, chloroform,aceton'itrile, dimethylformamide or N-rfiethyl-pyrrolidone, in thepresence of a strong base 1 such as an alkali metal alkoxide, forexample potassium nited States Patent 0 3,823,240 Patented July 9, 1974wherein R represents a hydrogen atom or an alkyl radical containing 1 to4 carbon atoms, and Ar, R and X are as hereinbefore defined. Thecyclisation can generally be efiected by heating in an organic solventin the presence of a basic condensation agent.

'llhe compounds of general formula IV can be obtained eit er:

(a) by the action of an acid or ester of the general formula:

(wherein R- X and R are as hereinbefore defined) on an aniline of thegeneral formula:

ArNH

(wherein Ar is as hereinbefore defined), or

(b) by the action of an amino-acid or ester of the general formula:

(wherein R and R are as hereinbefore defined) on a phenyl isocyanate orisothiocyanate of the general formula:

ArN= C=X VIII (wherein Ar and X are as hereinbefore defined) accordingto known methods for the preparation of ureas and thioureas.

According to another feature of the invention the hydantoin derivativesof general formula I, wherein R represents a grouping -NR R in which Rrepresents a hydrogen atom and R, represents an alkyl radical containing1 to 4 carbon atoms or an alkenyl radical containing 2 to 4 carbonatoms, are prepared by the process which comprises reacting anisocyanate of the general formula:

(wherein R represents an alkyl radical containing 1 t0 4 carbon atoms oran alkenyl radical containing 2 to 4 carbon atoms) with a hydantoincompound of general formula III by known methods for the preparation ofureas, for example by heating the reactants in an organic solvent suchas benzene or acetone in the presence of a basic condensation agent suchas triethylamine. By the term known methods is meant methods heretoforeused or described in the literature.

The hydantoin derivatives of general formula I obtained by theaforementioned processes may optionally be purified by physical methodssuch as crystallisation, distillation or chromatography.

The hydantoin derivatives of general formula I possess valuablefungicidal properties; they are particularly active against grey moulds(Botrytis cinerea) bean anthracnose (Colletotrichum lindemuflzianum) andsclerotinia rot (Sclerotinia sclerotiorum) when used in quantitiesbetween 25 and g. per hectolitre of, for example, water. They areparticularly intersting for the treatment of vines, strawberry plants,fruit trees (e.g. peach, apricot and cherry trees) and market gardeningproduce (e.g. vegetables for salids) to control fungal infections.Preferred compounds are those in which Ar represents the phenyl radicalor a phenyl radical carrying one or two substituents selected fromchlorine and fluorine atoms, alkyl radicals containing 1 to 4 carbonatoms (preferably methyl) and the trifluoromethyl radical, and moreparticularly those compounds wherein Ar represents the3,5-dichlorophenyl radical, R represents a grouping NR R in which Rrepresents a hydrogen atom and R represents an alkyl radical containing1 to 4 carbon atoms or an alkenyl radical containing 2 to 4 carbon atoms(preferably allyl), and R and X are as hereinbefore defined. Ofoutstanding importance are l-propylcarbamoyl-3 (3 S-dichlorophenyl)hydantoin, 1-allylcarbam0yl-3- 3 ,5 -dichlorophenyl hydantoin,1-isopropylcarbamoyl-3- 3 ,5 -dichlorophenyl) hydantoin, .l-methylcarbamoyl-3 3 S-dichlorophenyl) hydantoin, 1-ethylcarbamoyl-3-3,5-dichlorophenyl hydantoin, 1-methylcarbamoyl-3- (3 ,5-dichlorophenyl) -2-thiohydantoin and l-ethylcarbamoyl-3 (3 5-dichlorophenyl -2-thiohydantoin.

The present invention also includes within its scope fungicidalcompositions which comprise, as the active ingredient, at least onehydantoin derivative of general formula I in association with one ormore diluents or adjuvants compatible with the hydantoin derivative(s)and suitable for use in agricultural fungicidal compositions. Thesecompositions can optionally contain other compatible pesticides, such asinsecticides or fungicides (e.g. maneb). Preferably the compositionscontain between 0.005% and 80% by weight of hydantoin derivative.

The compositions may be solid if there is employed a powdered solidcompatible diluent such as talc, calcined magnesia, kieselguhr,tricalcium phosphate, powdered cork, adsorbent charcoal, or a clay suchas kaolin or bentonite. These solidc ompositions are preferably preparedby grinding the hydantoin derivative with the solid diluent, or byimpregnating the solid diluent with a solution of the hydantoinderivative in a volatile solvent, evaporating the solvent, and ifnecessary grinding the product so as to obtain a powder.

Instead of a solid diluent, there may be used a liquid in which thehydantoin derivative is dissolved or dispersed. The compositions maythus take the form of suspensions,

. emulsions or solutions in organic or aqueous-organic media, forexample aromatic hydrocarbons such as toluene or xylene, mineral, animalor vegetable oils, anisole, cyclohexanone or acetophenone, or mixturesof these diluents. The compositions in the form of suspensions,emulsions or solutions may contain wetting, dispersing o emulsifyingagents of the ionic or nonionic type, for example sulphoricinoleates,quaternary ammonium derivatives or products based on condensates ofethylene oxide, such as the condensates of ethylene oxide withoctylphenol, or fatty acid esters of anhydrosorbitols which have beenrendered soluble by etherification of the free hydroxy groups bycondensation with ethylene oxide. It is prefrable to use agents of thenon-ionic type because they are not sensitive to electrolytes. Whenemulsions are required, the hydantoin derivatives may be used in theform of self-emulsifying concentrates containing the active substancedissolved in the emulsifying agent(s) or in a solvent containing theemulsifying agent(s) compatible with the hydantoin derivative andsolvent, a simple addition of water to such concentrates producingcompositions ready for use. I

: .The hydantoin derivatives of general formula I are preferablyemployed as fungicides in quantities of to 200 g. per hectolitre ofwater, and in the field at the rate of about 1,000 litres of solutionper hectare under cultivation.

.7 The following Examples illustrate the invention.

EXAMPLE 1 toin (12.3 g.) in benzene (150 cc.). After azeotropicdistillation of the ethanol, methyl chloroformate (6.6 g'.) is added andthe reaction mixture heated for 10 minutes under reflux. The benzene isthen evaporated under reduced pressure and the residue is recrystallisedfrom ethanol to yield 1-methoxycarbonyl 3-phenylhydantoin (11 g.)melting at 154 C.

3-Phenylhydantoin, m.p. 156 C.,' employed "as starting material can beprepared accordingto the, method described by Dains, J. Amer. Chem.Soc., 44, 2312 (1922).

By proceeding as described above .but starting with appropriatecompounds of general formulae II and. IILthere are obtained thefollowing products:

10. 1-methoxyearbonyl-3-(3,5-dimethylphenyDhydantoin.,

EXAMPLE 11 A 22.5% (w./v.) ethanolic solution of potassium ethoxide (26cc.) is added to a suspension of 3-(3-chlorophenyl)hydantoin (14 g.) inbenzene (200 cc.). After azeotropic distillation of the ethanol,dimethylcarbamoyl chloride (7.2 g.) is added and the reaction mixtureisheated for 10 minutes under reflux. The precipitate which forms isfiltered off and the benzene is evaporated under reduced pressure. Theresidue obtained is Washed successively with anaesthetic grade diethylether (50 cc.) and petroleum ether (b.p. 5070 C.; 50 cc.) to yield 1-dimethylcarbamoyl 3 (3 chlorophenyl)hydantoin (7.8 g.) melting at 152 C.

3-(3-Chlorophenyl)hydantoin, m.p. 143 C., employed as starting materialcan be prepared according to the method described by Dains, J. Amer.Chem. Soc.,j44, 2312 (1922). e

EXAMPLE 12 Allyl isocyanate (4.5 g.) and triethylamine (5.5 g.) areadded to a solution of 3-(3,5-dichlorophenyl)-hydantoin (11 g.)) inacetone (150 cc.). After30 minutes heating under reflux followed bycooling, the acetone is evaporated under reduced pressure. The residueobtained is washed with petroleum ether (b.p. 50-70 C.; 250cc.) andrecrystallised from ethanol to yield l-allylcarbamoyl-3-(3,S-dichlorophenyl)hydantoin (11 g.) melting' at 116 C.

3-(3,5-Dichlorophenyl)hydantoin, m.p. 199 v.C., employed as startingmaterial can be prepared according to the method described by Dhar, J.Soc. Ind. Research, 20c, 145 (1961).

EXAMPLE 13 Propyl isocyanate (4.6 g. and triethylamine (5.5 g.)

are added to a solution of 3-(3,5-dichlorophenyl)-hydantoin (11 g.) inacetone (150 cc.) After 30 minutes A 22.5% (w./v.) ethanolic solution ofpotassium ethoxide,(3 2 cc.) is added to a suspension of3-phenylhydanheating under reflux following by cooling, the acetone: isevaporated under reduced pressure.,The residue. obtained is washed withpetroleum ether (bjpl 50 -'70 ,C.; 250cc.) and recrystallised from.diisopropyl ether; {to yield. 1- propylcarbamoyl 3 (3,5dichlorophenyDhydantoin (11 g.) meltingat92 C. T

Melting point Product C.)

'l-isopropylcarbamoyl-3-(3 chlorophenyl)hydantoin. 109

- ropylcarbamoylBAiS-chlorophenyl)hydantoin 90 y-methylcarbamoyl-3(3,5-dichlorophenyl)hydantoin 163 Lethylcarbamoyl31(3,5-qtchlorophenyl)hydantoin 152 18l-methylcarbamoyl-3-(3-chloropheny1)-5-methyl- 130 hydantoin.

i:19 l.-isopropylcarbamoyl-3 (3,5 dichlorophenyDhydantoin 136 201-butylcarbamoy1-3-(3,5 dichlorophenyl)hydantoim 112 211-isopropy1carbamoyl-3-(3,5dieli1orophenyD-5- 125 22 Il-ethylcarbamoyl-B-(3-fluorophenyiJhydanto1n 140 23; 2 lpropylcarhamoyw- (3-1luoropheh yl)hydantoin 93 241-methylcarbamoyl-3-(3;trifluoromethy1phenyl)- 120 hydantoin. 207

25 l-methylcarbamoyl 3-(3-fiuorophenyl)hydantoin EXAMPLE 26 Methylisocyana'te 3.4g and'triethylamine (4 g.) ,are added to a suspension of3-(3,5-dichlorophenyl)-5- methylliydantoin (10.4 g.) in benzene (150cc.). After heating for 1 hour under reflux followed by cooling, thebenzene is evaporated under reduced pressure. The residue obtained iswashed with anaesthetic grade diethyl ether (30 cc.) and petroleum ether(b.p. 5070 C.; 200 cc.) and recrystallised from ethanol to yieldl-methylcarbamoyl 3 (3,S-dichlorophenyl)e methylhydantoin (9 g.) meltingat 137 C.

3 (3,5 Dichlorophenyl) S-methylhydantein, m.p. 156 C., employed asstarting material can be prepared according to the method described byDhar, J. Soc. Ind. Research, 20c, 145 (1961).

By proceeding as described above but starting with appropriate compoundsof general formulae III and IX there are obtained the followingproducts:

EXAMPLE 29 Methyl isocyanate (3.4 g.) and triethylamine (5 g.) are addedto a solution of 3-(3,5-dimethylphenyl)-hydantoin (10.2 g.) in acetone(120 cc.). After leaving the reaction mixture to stand for 24 hours at atemperature of about 20 C., the precipitate which forms is filtered offand dried in vacuo over sulphuric acid. There is thus obtained 1methylcarbamoyl 3-(3,5-dimethylphenyl)hydantoin (11 g.) melting at 204C.

3 (3,5 Dimethylphenyl)hydantoin, m.p. 128 C., employed as startingmaterial can be prepared according to the method described by Dhar, J.Soc. Ind. Research, 200, 145 (1961).)

EXAMPLE 30 A 22.5% (w./v.) ethanolic solution of potassium ethoxide (13cc.) is added to solution of 3-phenyl-2-thiohydantoin (6.8 g.) inN-methylpyrrolid-2-one 150 cc.). After distillation of the ethanol underreduced pressure,

. ethyl chloroformate (3.8 g.) is added and the reaction mixture stirredfor 5 hours at about 25 C. A small amount of insoluble material isseparated by filtration and the filtrate poured into ice-water (500cc.). The precipitate which forms is filtered off and recrystallisedfrom ethanol to yield 1 othoxycarbonyl 3 phenyl-2-thiohydantoin (4.2 g.)melting at 142 C.

3-Phenyl-2-thiohydantoin, m.p. 242 C., employed as starting material canbe prepared according to the method described by Aschan, Ber., 17, 424((1884).

By proceeding as described above but starting with appropriate compoundsof general formulae II and 111 there are obtained the followingproducts:

dantoin.

EXAMPLE 33 Methyl isocyanate (3.2 g.) and triethylamine (0.5 cc.) areadded to a suspension of 3-(3-chlorophenyl)-2-thiohydantoin (7 g.) inbenzene cc.). After heating for 2 hours under reflux followed bycooling, the precipitate which forms is filtered off, washed withdiisopropyl ether (2X 50 cc.) and dried in vacuo over sulphuric acid.There is thus obtained 1 methylcarbamoyl 3 (3chlorophenyl)-Z-thiohydantoin (6.7 g.) melting a 170 C.

3-(3-Chlorophenyl) 2 thiohydantoin, m.p. 216 C., employed as startingmaterial can be prepared according to the method described by Dains, J.Amer. Chem. Soc., 44, 2312 (1922).

By proceeding as described above but starting with appropriate compoundsof general formulae III and IX there are obtained the followingproducts:

EXAMPLE 36 A 22.5% (w./v.) ethanolic solution of potassium ethoxide(15.4 cc.) is added to a solution of 3-(3,5-di chlorophenyl) 2thiohydantoin (10.4 g.) in dimethylformamide cc.). After removal of theethanol by distillation, dimethylcarbamoyl chloride (4.3 g.) is added.After leaving the reaction mixture overnight at a temperature of about20 C., the reaction mixture is poured into water (1,500 cc.) and theprecpitate which forms is extracted with methylene chloride (1,000 cc.).After chromatography through a column of Florisil (an activatedmagnesium silicate) and recrystallisation from toluene, there isobtained 1 dimethylcarbamoyl 3 (3,5 dichlorophenyl)-2-thiohydantoin (1.6g.) melting at 216 C.

3-(3,5 Dichlorophenyl) 2 thiohydantoin, m.p. 258 C., employed asstarting material can be prepared according to the method described byDains, J. Amer. Chem. Soc., 44, 2313 (1922).

EXAMPLE 37 In accordance with a usual technique there is prepared anemulsifiable solution having the following composition:

l-propylcarbamoyl 3 (3,5-dichlorophenyl)hydantoin 400 Tween 20 10 Altox4855 90 Cyclohexanone-xylene mixture (1-3 by volume) quantity to make upto 1,000 cc.

EXAMPLE 38 In accordance with a usual technique there is prepared anemulsifiable solution having the following composition:

Anisole, quantity to make up to 1,000 cc.

Tween 20 is a wetting agent which is a condensate of ethylene oxide withfatty acid esters of sorbitol, and Atlox 4855 is an emulsifying agentwhich is a polyoxyethylene derivative of an arylsulphonate.

I claim:

1. A fungicidal composition comprising as the active ingredient ahydantoin derivative of the formula:

N Raj \FX N-Ar wherein Ar represents phenyl or phenyl substituted withone to two substituents selected from the group consisting of chlorine,fluorine, alkyl of 1 to 4 carbon atoms and trifluoromethyl; R representsalkoxy of 1 to 4 carbon atoms or NR R in which R and R representshydrogen, alkyl of 1 to 4 carbon atoms or alkenyl of 2 to 4 carbonatoms; R represents hydrogen or alkyl of 1 to 4 carbon atoms; and Xrepresents oxygen or sulphur in association with one or more diluentscompatible with said hydantoin derivative and suitable for use inagricultural fungicidal compositions, the amount of hydantoin derivativein the composition being between 0.005% and 80% by weight of thecomposition.

2. The composition of claim 1 in which, in the said hyantoin derivative,Ar represents 3,5-dich1orophenyl and R represents -NHR in which Rrepresents alkyl of 1-4 carbon atoms or alkenyl of 2-4 carbon atoms.

'8 3. The composition of 1 claim 1, wherein said hydantoin derivative is1 propylcarbamoyl 3 (3,5 dichlorophenyl)hydantoin. r

4. The composition of claim 1, wherein said hydantoin derivative is 1allylcarbamoyl 3' (3,5 dichlorophenyl)hydantoin.

5. The composition of claim 1, wherein said hydantoin derivative is 1isopropylcarbamoyl 3 (3,5 dichloro- PhenyDhydantoin. 1:

6. The composition of claim 1, wherein said hydantoin derivative is 1methylcarbamoyl -.;-3 (3,5 .--:dichlorophenyl)hydantoin. V r 7. Thecomposition of claim 1, wherein said hydantoin derivative is 1ethylcarbamoyl 3 (3,5 dichloropheny1)hydantoin. 8. The composition ofclaim 1, wherein saidhydantoin derivative is 1 methylcarbamoyl -'3 (3,5dichloro'- phenyl)-2-thiohydantoin. V p W 4 Y f 9. The composition ofclaim 1, wherein said hydantoin derivative is 1 ethylcarbamoyl- 3 (3,5dichlorophenyl)-2-thiohydantoin.

References Cited UNITED STATES PATENTS 3,300,510 1/1967 Alburn et al.260-3095 3,681,377 8/1972 .Singhal 260-3095 ALBERT T. MEYERS, PrimaryExaminer I L. SCHENKMAN, Assistant Examiner

